Are withanolides good for you? Exploring the health benefits and risks

November 6, 2025 •

4 min read

Ashwagandha, the source of withanolides, has been used in Ayurvedic medicine for thousands of years to promote overall wellness. Withanolides, the active compounds within this adaptogenic herb, are drawing modern scientific attention for their potential benefits in supporting mental health, reducing inflammation, and boosting the immune system. But are withanolides good for you in practice?

Quick Summary

Withanolides from ashwagandha are studied for potential benefits including stress reduction, anti-inflammatory effects, and cognitive support. Research suggests these compounds influence key biological pathways in the body.

Key Points

Stress & Anxiety Relief: Clinical trials show withanolides help lower stress and anxiety, likely by modulating cortisol levels and the HPA axis.
Sleep Improvement: Ashwagandha extracts containing withanolides have been found to improve overall sleep quality and help reduce sleep onset latency.
Anti-inflammatory Effects: Withanolides, particularly withaferin A, exhibit potent anti-inflammatory properties by modulating key signaling pathways like NF-κB.
Neuroprotection: Preclinical studies indicate that withanolides may protect against oxidative damage and support cognitive functions such as memory and attention.
Immune and Athletic Support: Withanolides show immunomodulatory and adaptogenic effects, potentially boosting the immune system and enhancing physical performance in athletes.
Potential Side Effects: Reported side effects are typically mild digestive issues, but more serious concerns exist regarding thyroid function, liver health, and interactions with other medications.
Standardized Extracts Matter: The concentration and source of withanolides vary significantly between supplements, with well-researched options like KSM-66 offering high standardization and known safety profiles.

Withanolides are a class of naturally occurring steroidal lactones found primarily in the adaptogenic herb Withania somnifera, also known as ashwagandha. As the main bioactive components of ashwagandha, they are believed to be responsible for many of its therapeutic effects. The name comes from the plant’s botanical classification and the unique lactone ring structure of these compounds.

What do withanolides do to the body?

Withanolides exert their effects by interacting with various physiological systems. They act as modulators, helping the body restore balance and respond more resiliently to stress. This is achieved through several mechanisms, including:

Modulating the HPA Axis: Withanolides help regulate the hypothalamic-pituitary-adrenal (HPA) axis, which is the body's primary stress response system. By reducing the activity of this axis, they help lower cortisol levels, a key stress hormone.
Neurotransmitter Regulation: These compounds influence neurotransmitter systems, such as GABAergic and cholinergic pathways, which contributes to their anxiolytic (anxiety-reducing) and cognitive-enhancing properties.
Targeting Inflammatory Pathways: Withanolides, particularly withaferin A (WA), have been shown to target multiple inflammatory signaling pathways, including NF-κB and JAK/STAT, to reduce inflammation.

Health benefits supported by research

Research has explored several potential health benefits associated with withanolides, predominantly through studies on ashwagandha extracts standardized for these compounds.

Stress and Anxiety Reduction

Multiple clinical trials suggest that ashwagandha extracts, standardized for withanolides, can significantly reduce perceived stress and anxiety levels. Participants in these studies often report improved well-being and reduced fatigue, alongside measurable reductions in serum cortisol levels. For example, a 2021 review found ashwagandha significantly reduced anxiety levels in several clinical trials compared to a placebo.

Improved Sleep Quality

For those struggling with insomnia and restless sleep, withanolides may offer a natural remedy. Studies have shown that ashwagandha extracts can improve overall sleep quality, reduce sleep onset latency (the time it takes to fall asleep), and promote better sleep efficiency. This sedative effect is linked to the modulatory influence of withanolides on the nervous system.

Anti-inflammatory and Immunomodulatory Effects

Withanolides possess potent anti-inflammatory properties, with preclinical studies demonstrating their ability to reduce levels of inflammatory proteins. Withaferin A, one of the most studied withanolides, modulates key cellular pathways involved in inflammation. Some studies also suggest withanolides act as immunomodulators, helping to boost the immune system. However, more human research is needed in this area.

Cognitive and Neuroprotective Benefits

Preclinical and limited clinical studies point to the neuroprotective effects of withanolides. They have shown potential in animal models for protecting neural tissues from oxidative damage, promoting neurite outgrowth, and augmenting cholinergic neurotransmission. This suggests a role in supporting memory, attention, and potentially combating neurodegenerative conditions, though further research is required to confirm these effects in humans.

Athletic Performance Enhancement

Some research indicates that withanolides may improve athletic performance. A review of studies found that ashwagandha can enhance physical performance metrics such as strength and maximum oxygen consumption (VO2 max) in both athletes and healthy adults. This is partly attributed to its adaptogenic and anti-inflammatory effects, which help the body cope with physical stress.

Potential side effects and safety concerns

While generally considered safe for short-term use (up to 3 months), several safety considerations and potential side effects are associated with withanolides.

Digestive Issues: Common mild side effects include stomach upset, nausea, loose stools, and diarrhea.
Thyroid Function: Withanolides may increase thyroid hormone levels, which could be problematic for individuals with thyroid disorders.
Liver Function: Rare cases of liver injury have been reported in individuals taking ashwagandha, though the connection is not always clear due to other factors.
Pregnancy and Breastfeeding: Ashwagandha, and by extension withanolides, should be avoided during pregnancy and breastfeeding due to potential risks.
Medication Interactions: Withanolides can interact with certain medications, including sedatives, immunosuppressants, and blood pressure or blood sugar medication.

Comparison of Ashwagandha Extracts with varying withanolide content

To illustrate the difference between standardized ashwagandha products, here is a comparison of two well-known extracts that contain withanolides.


Feature	KSM-66 Ashwagandha	Sensoril Ashwagandha
Sourcing	Extracted from roots only.	Extracted from both leaves and roots.
Standardization	Standardized to a minimum of 5% withanolides.	Standardized to a minimum of 10% withanolide glycosides.
Withaferin A Content	Negligible concentration of this specific withanolide.	Standardized to less than 0.5% Withaferin A.
Safety Profile	Considered safe and effective with extensive research.	Well-researched and considered safe when Withaferin A is standardized low.

Conclusion: So, are withanolides good for you?

Overall, the benefits of withanolides appear to outweigh the risks for most healthy adults seeking support for stress, anxiety, sleep, and athletic performance. However, the quality and standardization of supplements are critical for both efficacy and safety, with some reports noting potential liver or thyroid issues. While promising, it is crucial to consult a healthcare professional before starting any new supplement, especially if you have pre-existing conditions or are taking other medications. The future of withanolide research holds promise for more targeted therapeutic applications.

Frequently Asked Questions

Withanolides are a group of naturally occurring steroidal lactones. They are the primary active compounds found in the Withania somnifera plant, most commonly known as ashwagandha.

Withanolides act as adaptogens, helping the body cope with stress by modulating the hypothalamic-pituitary-adrenal (HPA) axis and reducing serum cortisol levels, a key stress hormone.

Yes, some research suggests that ashwagandha extracts rich in withanolides can improve sleep quality, reduce the time it takes to fall asleep, and enhance overall sleep efficiency.

Preclinical studies show that withanolides, especially withaferin A, possess strong anti-inflammatory properties by inhibiting pathways like NF-κB. Limited human studies have also shown a reduction in inflammatory markers.

Withanolides should be avoided by pregnant and breastfeeding women. Individuals with thyroid issues, liver disease, or those on certain medications for blood pressure, blood sugar, or immunosuppression should consult a doctor before use.

KSM-66 is an extract from ashwagandha roots only, standardized to 5% withanolides, with very low withaferin A. Sensoril is an extract from both leaves and roots, standardized to at least 10% withanolide glycosides and less than 0.5% withaferin A.

While generally well-tolerated for short periods, some people may experience mild side effects like digestive upset, nausea, or drowsiness. More serious but rare side effects involve liver or thyroid function, and they can interact with medications.